Metabolic Disorders and Screening 1 and 2

Question 1

What are the criteria for screening programmes called?

Answer 1

Wilson and Junger

Question 2

What causes Phenylketonuria (PKU)?

Answer 2

Deficiency of phenylalanine hydroxylase

Question 3

What does phenylalanine do?

Answer 3

Converts phenylalanine to tyrosine

Question 4

What are key clinical features of PKU?

Answer 4

Low IQ
Seizures
Stunted growth
Hyperactivity
Musty odor of breath/skin/urine

Question 5

How is PKU treated?

Answer 5

Monitor diet closely
Monitor phenylalanine intake
Treatment must be started within first 6 weeks of life

Question 6

What is sensitivity?

Answer 6

True positives/total number of disease cases

Question 7

What is specificity?

Answer 7

True negatives/total number without the disease

Question 8

What is the positive predictive value?

Answer 8

True positives/total number with positive results

Question 9

What is the Guthrie test and when is it done?

Answer 9

UK Newborn Screening
Heel prick test
Blood sample to screen for abnormalities
5-8 days of life

Question 10

What illnesses are in the Newborn screening programme?

Answer 10

Congenital hypothyroidism
Sickle cell disease
Cystic fibrosis
A series of metabolic disorders:
MCAD deficiency
Maple syrup urine disease
Isovaleric acidaemia
Glutaric aciduria type 1
Homocystinuria

Question 11

What is MCAD deficiency?

Answer 11

Fatty acid oxidation disorder

Question 12

What does MCADD classically result in?

Answer 12

Cot death due to hypoglycaemia

Question 13

What gene is affected in cystic fibrosis?

Answer 13

Cystic fibroiss transmembrane conductance regulator (CFTR)

Question 14

What test is used to screen for CF?

Answer 14

High immune reactive trypsinogen

Question 15

What mutation most commonly causes CF?

Answer 15

Delta F508

Question 16

What is the urea cycle responsible for?

Answer 16

Breaking down ammonia into urea

Question 17

How many enzymes are in the urea cycle?

Answer 17

7

Question 18

What is the genetic inheritance of urea cycle disorders?

Answer 18

Autosomal recessive except ornithin transcarbamylase (OTC) deficiency which is X-linked

Question 19

How does the body react to hyperammonimia?

Answer 19

Attach glutamine to ammonia to make glutamine

Question 20

What can be measured in the urine to look for urea cycle disorders?

Answer 20

Orotic acid

Question 21

How are urea cycle disorders treated?

Answer 21

Remove the ammonia: sodium benzoate, sodium phenylacetate, or dialysis
Reduce ammonia production: low protein diet

Question 22

With what groups of condition can hyperammonaemia be associated?

Answer 22

Long-term psychiatric illness

Question 23

What are key features of urea cycle disorders?

Answer 23

Vomiting without diarrhoea
Respiratory alkalosis
Hyperammonaemia
Neurological encephalopathy
Avoidance of protein

Question 24

What is an organic aciduria?

Answer 24

A defect within the complex metabolism of branched chain amino acids (leucine, isoleucine, and valine)

Question 25

What are the amino acids excreted as in organic aciduria?

Answer 25

3-OH-isovaleric acid (cheesy/sweaty smell) | Isovaleryl glycine

Question 26

How does a neonate present with organic aciduria?

Answer 26

``` Unusual odour Lethargy Feeding problems Truncal hypotonia Myoclonic jerks Hyperammonaemia with metabolic acidosis and high anion gap ```

Question 27

What is Reye's syndrome?

Answer 27

``` A rare disorder causing swelling of the brain and liver. Features include: - Vomiting - Lethargy - Confusion - Decerebration - Respiratory arrest ``` Can be triggered by drugs (salicylates) and viral illness.

Question 28

What is included in a Reye Syndrome metabolic screen?

Answer 28

``` During acute episode: Plasma ammonia Plasma/urine amino acid Urine organic acids Plasma glucose and lactate ``` Any time: Blood spot carnitine profile

Question 29

What do mitochondrial fatty acid beta-oxidation defects cause?

Answer 29

Hypoketotic hypoglycaemia - unable to break down fatty acids

Question 30

What do mitochondrial fatty acid beta-oxidation disorders do to the body?

Answer 30

Hepatomegaly | Cardiomyopathy

Question 31

How many disorders of galactose metabolism are there?

Answer 31

3

Question 32

What is the most common and severe form of galactose metabolism?

Answer 32

Galactose-1-phosphate uridyl transferase deficiency

Question 33

What key feature to children galactose-1-phosphate uridyl transferase deficiency present with?

Answer 33

Conjugated hyperbilirubinaemia

Question 34

What complication can occur in children if galactose-1-phosphate uridyl transferase deficiency is not picked up on?

Answer 34

Bilateral cataracts

Question 35

How is mitochondrial DNA inherited?

Answer 35

Maternally

Question 36

What does heteroplasmy mean?

Answer 36

You need a certain load of mitochondrial DNA to develop symptoms